Pharmacogenetics of chlorpromazine and its role in the development of antipsychotic-induced parkinsonism

Antipsychotics (AP) is a group of psychotropic drugs for the treatment of mental disorders, in particular schizophrenia. In the mid-1950s, the first AP was synthesized (known as chlorpromazine (CPZ)). This drug has revolutionized the treatment of psychotic disorders. This drug, in addition to the antipsychotic effect, caused severe adverse drug reactions in patients, in particular from the neurological system, such as AP-induced extrapyramidal syndrome (EPS) — chlorpromazine-in-duced parkinsonism (CPZ-IP). CPZ-IP characterized by the occurrence of motor disorders. CPZ-IP is as a result of damage to the basal ganglia and subcortical-thalamic connections. Drug-induced EPS is subdivided into primary and secondary. Among the primary EPS, drug-IP is the most common (the leading form of secondary parkinsonism). Pharmacogenetic markers of CPZ safety are being actively studied. Some pharmacogenetic markers of therapy safety have been established: single nucleotide variants/polymorphisms of candidate genes for dopaminergic receptors D2 and D3 (DRD2 (rs1799732 (-141C Ins/Del)), DRD3 (rs6280 (Ser9Gly)), laforine phosphatase (EPM2A (rs1415744 (C/T)).